U.S. Pat. No. 4,880,835 describes the preparation of oral liquid compositions of calcium sulindac using a pharmaceutical vehicle comprised of a glycol, a polyol and an optional alcohol. That patent describes the problems of absorption of drug from the gut which are present in the art.
K. Chan et al., Pharm. Research, 7 1027 (1990) demonstrated that sodium diclofenac was more bioavailable orally from an enteric coated tablet than from an aqueous solution. This is contrary to the expectation of the art and confirms the fact that a problem exists in the art. U.S. Pat. No. 4,704,405 also describes the problem of absorption of NSAID's from the gastrointestinal track, especially as applied to sulindac.
N. M. Najib et al., International Journal of Pharmaceutics, 45 139 (1988) has reported that ibuprofen-polyvinylpyrrolidone in contact may form a weak acid-weak base type of complex in the solid state or in solution. This reference does not report any studies in the glycol-polyol media of the present invention. Nor does there exist any suggestion in Najeb that a pharmaceutically elegant preparation of NSAID's which has exceptional behavior upon dispersion in gastric juice is formed by the use of certain selected dispersing agents.
U.K. Patent No. 2,059,768 describes the formation of more soluble derivatives of NSAID's with the TRIS group of compounds.
I have now confirmed that the oral liquid compositions of NSAID's which are described in U.S. Pat. No. 4,880,835, at best, equal the release of drug from ingestion of the solid pharmaceutical form on the market. Further, I have discovered that when NSAID's contained in liquid carriers contact acid gastric fluid, the drug forms a sticky agglomerate which separates from the acid supernatant liquid. The active NSAID agent, therefore, becomes available for absorption only by being broken up during mechanic agitation, an uncertain and unreliable method of delivery.